血红素加氧酶-1对重症急性胰腺炎大鼠模型胰腺和肝脏保护作用的实验研究

Protective effects of heme oxygenase-1 on pancreas and liver in rats with severe acute pancreatitis： in vivo study

目的探讨血红素加氧酶-1对重症急性胰腺炎大鼠胰腺、肝脏的作用及机制。方法将40只雄性SD大鼠编号后电脑随机抽取编号分组，分为正常组（10只）、SAP模型组（10只）、HO-1表达促进组（造模后30min腹腔注射牛血精素75μg／kg，10只）和HO-1表达抑制组（造模后30rain腹腔注射锌原卟啉20μg/kg，10只）。采用3％牛黄胆酸钠SAP模型，观察制模后24h胰腺、肝脏组织病理学变化并检测血清、胰腺和肝脏组织中的HO-1、IL-10、TNF—α含量。结果HO-1表达促进组的胰腺、肝脏组织的病理评分较SAP模型组显著降低[（7．50±0．58）vs（10．50±0．71）；（1．20±0．42）vs（1．70±0．48）]（P〈0．05）；并且其血清（0．97±0．02）ng／mL、胰腺（0．78±0．09）ng／mL和肝脏组织（0．73±0．05）ng/mL的HO-1含量和IL—10[（101．72±2．63）ng／mL，（63．58±1．02）pg／mL，（169．40±3．06）pg／mL]含量较SAP模型组均显著升高（P〈0．05），而血清（22．85±1．74）Pg／mL、胰腺（26．50±1．3）pg／mL和肝脏（35．88±0．98）pg／mL组织的TNF-α含量却显著下降（P〈0．05）。HO-1表达抑制组的胰腺、肝脏病理评分较SAP组显著升高，其血清、胰腺和肝脏的HO-1和IL-10含量显著降低（P〈0．05），而TNF-α却显著升高（P〈0．05）。结论研究结果显示，HO-1高表达对于SAP大鼠的胰腺和肝脏具有保护作用，提高IL-10表达和抑制TNF-α表达可能是其作用机制。

Objective To investigate the effects of heine oxygenase- 1 （ HO- 1 ） on pancreas and liver in severe acute pancreatitis（SAP） rats, and explore its probable mechanism. Methods A total of 40 male SD rats were randomLy divided into 4 groups： control group（ n = 10） ; SAP group（ n = 10） ; HO-1 stimulation group （ 75 μg/kg hemin was injected intraperitoneally at 30 minutes after model establishment, n = 10 ） ; HO- 1 inhibition group（20 μg/kg ZnPP was injected intraperitoneally at 30 minutes after model establishment, n = 10）. Sodium Cholate （3%） was retrogradedly injected into the pancreatic duct to produce the SAP model. To observe the histopathological changes of pancreas, liver tissues were observed and serum, pancrease and liver tissues concentration of HO-1, IL-10 and TNF-α in different groups were observed 24 h after the SAP model establishment. Results Compared with those in SAP model group, the pathological scores were lower in HO- 1 stimuLation group [ （ 7.50 ± 0. 58 ） vs （ 10.50 ± 0. 71 ） ; （ 1.20 ± 0. 42 ） vs （ 1.70 ± 0.48 ） ] （ P 〈 0. 05 ） ,and the serum, pancreas and liver tissues HO- 1 [ （0.97 ± 0. 02 ） ng/mL, （0.78 ± 0. 09 ） ng/ mL,（0.73 ±0.05） ng/mL] and IL-10[ （101.72 -±2.63） ng/mL, （63.58 ±1.02） pg/mL, （169.40 ± 3.06 ） pg,/mL] concentrations were significantly elevated in HO- 1 stimuLation group （ P 〈 0.05 ）, while the serum, pancreas and liver tissues TNF- α [ （ 22.85 ± 1.74 ） pg/mL, （ 26.50 ± 1.3 ） pg/mL, （ 35.88 ± 0.98） pg/mL] eoneentrations were significantly decreased in HO- 1 stimulation group （ P 〈 0. 05 ）. Compared with those in SAP model group, the pathological scores were higher in HO-1 inhibition group （P 〈 0. 05 ）, and the serum, pancreas and liver tissues HO-1 and IL-10 concentrations were significantly decreased （P 〈 0.05 ） , while the serum, pancreas and liver tissues TNF-α concentrations were significantly elevated （P 〈 0.05 ）. Conclusion The results of the study demonstrated that HO- 1 over- expression has protective effects on the pancreas and liver in SAP. UP-regulated IL-10 expression and down-reguLated TNF-α expression might be served as a potential mechanism.